BACKGROUND: Garlic supplements are the most consumed herbal products in the US. The most common health claims made for these products is that of cholesterol lowering. This claim has not been supported by 7 recent clinical trials and 2 recent meta-analyses. However, the data suggest that it is not garlic, per se, that has been ineffective, but the particular garlic preparations being used. To date, the type of garlic preparation used in these clinical trials has predominantly been dried garlic powders. A few clinical trials have reported beneficial lipid effects using an aged garlic extract, and only a small number of weak and inconclusive uncontrolled trials have used fresh garlic. A rigorous trial directly comparing different types of garlic preparations for their effects on serum lipids is needed. OBJECTIVE: To decisively determine whether fresh garlic can positively affect serum lipids in moderately hyperlipidemic adults and whether the same effects can be found for two main types of garlic supplements: a dried powdered garlic designed to yield the same bioactive agents in vivo as fresh garlic (GARLICIN) and an aged garlic extract preparation (KYOLIC). DESIGN: 220 adults with moderately elevated LDL-cholesterol (LDL-C) will be randomized to one of 4 groups for 6 months: fresh garlic, Garlicin tablets, Kyolic tablets, or Control. Both the fresh garlic and control groups will receive placebo tablets. The fresh garlic will be provided to participants with "study sandwiches," and all other groups will receive the same sandwiches, but without the garlic. The primary outcome will be 6-month changes in LDL-C levels. Secondary outcomes will include HDL-cholesterol, triacylglycerols, platelet function, antioxidant status and blood pressure. IMPLICATIONS: This investigation will address 1) the magnitude of the effect on serum lipids, 2) the debate over the most effective type of garlic preparation, and 3) previous criticisms as to the transience of the effect. The comprehensive approach taken in this study will provide important evidence for both the public and for health professionals as to whether fresh garlic or garlic supplements have beneficial effects on serum lipids.